2aq9

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spinqualitylabelsall models 2aq9, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Structure of E. coli LpxA with a bound peptide that is competitive with acyl-ACP

Overview

UDP-GlcNAc acyltransferase (LpxA) catalyzes the first step of lipid A, biosynthesis, the transfer of the R-3-hydroxyacyl chain from, R-3-hydroxyacyl acyl carrier protein (ACP) to the glucosamine 3-OH group, of UDP-GlcNAc. LpxA is essential for the growth of Escherichia coli and, related Gram-negative bacteria. The crystal structure of the E. coli LpxA, homotrimer, determined previously at 2.6 A in the absence of substrates or, inhibitors, revealed that LpxA contains an unusual, left-handed parallel, beta-helix fold. We now present the crystal structure at 1.8 A resolution, of E. coli LpxA in a complex with a pentadecapeptide, peptide 920. Three, peptides, each of which adopts a beta-hairpin conformation, are bound per, LpxA trimer. The peptides are located at the interfaces of adjacent, subunits in the vicinity of the three active sites. Each peptide interacts, with residues from both adjacent subunits. Peptide 920 is a potent, inhibitor of E. coli LpxA (Ki = 50 nM). It is competitive with respect to, acyl-ACP but not UDP-GlcNAc. The compact beta-turn structure of peptide, 920 bound to LpxA may open previously uncharacterized approaches to the, rational design of LpxA inhibitors with antibiotic activity.

About this Structure

2AQ9 is a Single protein structure of sequence from Escherichia coli with PO4 and DMS as ligands. Active as [acyl-carrier-protein--UDP-N-acetylglucosamine_O-acyltransferase Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase], with EC number 2.3.1.129 Full crystallographic information is available from OCA.

Reference

Structure of UDP-N-acetylglucosamine acyltransferase with a bound antibacterial pentadecapeptide., Williams AH, Immormino RM, Gewirth DT, Raetz CR, Proc Natl Acad Sci U S A. 2006 Jul 18;103(29):10877-82. Epub 2006 Jul 11. PMID:16835299 [[Category: Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase]]

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